Is NLRP14 p.Ser98Leu (c.293C>T) pathogenic?

NLRP14 p.Ser98Leu (c.293C>T) is classified Benign in NLRP14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-14). AlphaMissense: likely benign (0.0824); Low-frequency (popmax 4.87%, mid); Associated with NLRP14-related disorder.

What condition is associated with NLRP14 p.Ser98Leu (c.293C>T)?

NLRP14 p.Ser98Leu (c.293C>T) is associated with NLRP14-related disorder (ClinVar).

How common is NLRP14 p.Ser98Leu (c.293C>T) in the general population?

NLRP14 p.Ser98Leu (c.293C>T) is low-frequency (popmax 4.87%, mid) (gnomAD).

What do computational predictors say about NLRP14 p.Ser98Leu (c.293C>T)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

NLRP14 p.Ser98Leu

c.293C>T · rs117823353 · VCV3059218

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.87%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NLRP14-related disorder

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.31	GERP 0.14
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	16.16	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.87% Middle Eastern · 295/6,054 alleles

Filtering AF 4.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.24%

Overall 3.13% 50,372/1,611,794 alleles · low-frequency exomes 46,850/1,459,570 · genomes 3,522/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.87%	21
European (non-Finnish)	3.55%	28
Ashkenazi Jewishnot grpmax-eligible	3.36%	30
South Asian	2.9%	34
Remaining individualsnot grpmax-eligible	2.87%	35
Finnishnot grpmax-eligible	2.01%	50
Admixed American	1.74%	57
African / African-American	0.627%	160
East Asian	0.0223%	4,487

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NLRP14
Protein: p.Ser98Leu
Coding: c.293C>T
MANE Select: NM_176822
dbSNP: rs117823353
Type: single nucleotide variant
Location: chr11:7039717 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 98: a UniProt-annotated variant site (in); an α-helix

Full NLRP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NLRP14-related disorder

Similar variants

NLRP14 c.1958+6T>C Likely benign same condition
NLRP14 p.Ala432= Benign same condition
NLRP14 p.Asp12= Likely benign same condition
NLRP14 p.Asp3Gly Benign same condition
NLRP14 p.Cys750Tyr Likely benign same condition
NLRP14 p.Gln484= Likely benign same condition
NLRP14 p.Glu21Lys Likely benign same condition
NLRP14 p.Gly242Asp Benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nlrp14-p-ser98leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown